The Agency for Healthcare Research and Quality has invited grant applications for the purpose of understanding the comparative value of different strategies in the prevention and management of chronic illness in persons with multiple chronic conditions. In this application, "Optimizing Chronic Disease Prevention and Management in Advanced Dementia", we propose to study the effectiveness of medication prophylaxis for chronic illness in the medically complex population of nursing home (NH) residents with advanced dementia. Over half of the 1.6 million residents of US NHs have dementia, and those with advanced dementia have a prognosis comparable to that of metastatic breast cancer or stage IV heart failure. Our prior work shows that medications inappropriate in advanced dementia are used by almost 40% of NH residents with advanced dementia, and are continued in almost 20% of these patients in the last week of life. These agents such as lipid-lowering and osteoporosis drugs may not be consistent with goals of care, increase the risk of adverse drug events and drug-drug interactions, are costly, and contribute to polypharmacy. Efforts to improve prescribing in advanced dementia are hampered by a lack of studies examining medication effectiveness and drug withdrawal safety in this population. The goal of this R21 is to develop the infrastructure to systematically investigate the effectiveness and safety of strategies to reconsider medications for chronic non-dementia illnesses in NH residents with advanced dementia. We describe the first in a series of studies evaluating the comparative effectiveness of medications of questionable benefit in advanced dementia, in order to rationally prioritize therapy for this vulnerable and understudied population. A particular focus is on the evaluation of the prevalence, cost, and factors associated with using medications inappropriate in NH residents with advanced dementia, and in evaluating the clinical impact of the use and discontinuation of statins for cardiovascular disease in this population. Studies will utilize administrative claims data linked to federally- mandated NH resident assessment data from 2 large populations: 1) over 12,500 NH residents with dementia who received prescription services from a nationwide long term care pharmacy between 2005-2008;and 2) NH residents of 5 states (Minnesota, Massachusetts, Pennsylvania, California and Florida), including ~95,000 NH residents with dementia who used Medicare Part D drug benefits between 2006-2007. Data sources for these populations include: drug claims for all dispensed medications;resident demographics;hospitalization claims;NH facility characteristics and mortality. Analyses will adapt techniques to address selection bias in observational studies (propensity scores, comparator group restriction, and self-controlled case-series), and methods for longitudinal and clustered data to account for repeat prescriptions in the same residents within NHs. These studies advance analytic strategies for evaluating prescribing strategies and their effects on NH residents with advanced dementia and lay the foundation for efforts to optimize prescribing in this population. PUBLIC HEALTH RELEVANCE: Project Narrative An estimated 1.8 million people in the United States are living with advanced dementia and are unable to recognize family, unable to communicate, and are physically dependent in activities of daily living. These patients use excessively complex medication regimens without good evidence that doing so will improve their survival or quality of life. Since unnecessary and inappropriate medication use in this population increases the risk of injury from adverse drug events and contributes to rising healthcare costs, comparative effectiveness studies are necessary to improve prescribing by examining medication effectiveness and drug withdrawal safety in this vulnerable and understudied population.